Almost every person in his or her lifetime will have taken some sort of drug, whether this is caffeine, nicotine or perhaps a recreational drug, such as cocaine. The taking of drugs seems to be a natural phenomenon within humans because as well as targeting the reward pathway within the brain, they provide an effect that is appealing to people; whether this is just a caffeine kick or the euphoria produced that allows people to escape from their usual way of thinking. The reward pathways within the brain are an evolutionary advantage that ensures that when a positive action is carried out (such as drinking water, eating food or having sex) it is repeated. Drugs target this pathway producing reinforcing affects. They do this by releasing dopamine, a neurotransmitter that activates the reward pathway, making the brain believe the effects of taking the drug are good, ‘rewarding’. In this article I will be talking about the reinforcing effects of cocaine, alcohol (ethanol) and nicotine.
The Reward Pathway:
First the terms ‘rewarding’ and ‘reinforcing’ require definition. A rewarding stimulus is one in which, through activation of dopamine, the brain understands to be not only positive but a stimulus that must be approached. Reinforcement means that the action produces the increasingly intense feeling that repetition is necessary. The pathways within the brain that induce reinforcement are a set of forebrain structures, connected through a series of neural pathways. These include the nucleus accumbens (which is part of the ventral striatum), the basal forebrain (which includes the amygdala) and regions within the medial prefrontal cortex (Eric J. Nestler et al, 2001). These areas of the brain receive dopaminergic innervation from the ventral tegmental area (which is part of the midbrain). Reinforcing drugs induce a sense of reward by increasing that release of dopamine within these forebrain structures, via activation of the mesocorticolimbic dopaminergic system. The euphoric state of the drug also plays a role in their reinforcing nature, but without this release of dopamine they would not necessarily be addictive. This is seen in LSD which does not provide this rapid onset of positive reinforcement, so although the drug does produce a state of euphoria, this alone is not enough to cause chronic use and abuse (Eric J. NEstler et al, 2001).
The mesocorticolimbic pathway originates in the ventral tegmental area of the midbrain and the dopaminergic neurone efferents that synapse in the ventral tegmental area are the most important in reinforcement.
Figure 1: The dopaminergic pathways of the brain.
Source: Bear et al., Neuroscience, 3rd edition.
Cocaine is a psychostimulant which produces a state of euphoria that induces a state of extreme pleasure and gratification, which is accompanied by a separation from reality. Cocaine is highly addictive due to its capability to produce strong reinforcement. Cocaine’s affects are fast acting but short lasting which also adds to its reinforcing nature, and is why users will continuously take the drug throughout a short period of time. Although cocaine is reinforcing, addicts of cocaine are more likely to go through sessions of binges on the drug rather than continual use. This may be due to the fact that withdrawal of cocaine does not necessarily produce major adverse effects on the body, (although there are emotional withdrawal symptoms) such as the shakes that would cause users to need the drug to function normally. The psychostimulant effects of cocaine results from the increased level of monoamine neurotransmitter release, including: dopamine, serotonin and noradrenaline. Cocaine targets the reuptake proteins of these neurotransmitters, binding to them and antagonising them, inhibiting their action. This decreases the amount of neurotransmitter being removed from the synaptic cleft, causing an increased level of neurotransmitter and enhancing the response. The prevention of the removal of dopamine is the most important for the reinforcing nature of cocaine. Dopamine release is increased in the nucleus accumbens.
Ethanol is a depressant within the central nervous system. This does not mean that taking alcohol makes the users depressed; in fact most of us know this is quite the contrary as alcohol usage is associated with increased happiness and a loss of social awkwardness, perhaps why people find it so pleasurable. What ‘depressant’ means in the case of ethanol is that it facilitates the action of GABAA receptors and inhibits glutamatergic NMDA receptors (Eric J. Nestler et al, 2001). The release of GABA within the brain acts to hyperpolarize the cell, making it more negative on the inside and decreasing the amount of action potential (hence depression). Glutamate is the main excitatory neurotransmitter within the brain and its release causes an increase in action potential firing. By inhibiting this, ethanol is again reducing the amount of action potential firing within the brain. If high doses of ethanol are taken then most ligand and voltage gated ion channels are affected. This is why alcohol has such a wide spread affect within the brain. The reinforcing nature of ethanol is not understood completely but is thought to be due to its effects on the NMDA receptors and its ability to activate the mesocorticolimbic pathway, although it is not yet know whether this reinforcing effect takes place in the ventral tegmental area or the nucleus accumbens. How dopamine is realised due to ethanol is also not confirmed as it could either be due to the facilitation of GABAA receptors or due to the inhibition of NMDA receptors (Eric J. Nestler et al, 2001). What is clear though it that one or both of these mechanism plays a role in inhibiting the tonic inhibition of the release of dopamine. Ethanol also reduces serotonergic function, which is thought to add to the reinforcing nature of ethanol. The fact that ethanol does affect so many systems within the brain is probably the main reason why it is so hard to find out why the drug is reinforcing, but it must be remembered that in many cases of drug abuse (this is very different from drug use) people are wanting to remove themselves from reality due to some underlying cause, and for some people this may be what motivates them to abuse alcohol or any other drug to such an extent.
Nicotine is the addictive substance within the Tabaco plant and within cigarettes, and now also E-cigarettes. Nicotine is an interesting drug, firstly because it is highly addictive although it does not cause any state of euphoria, showing how this drugs addictive nature is so much to do with how it’s affects on the central and peripheral nervous system. Secondly, as most of us know smoking is not pleasurable and in fact quite deterring the first couple of times people smoke, and it must be taken quite frequently to become pleasurable. This shows how drug taking can be so associated to one’s social environment as without this most people would not force themselves to continue smoking. It is also shown in animal studies that the animals will not choose to take nicotine if they have the choice (Eric J. Nestler et al, 2001). Therefore the reinforcing nature of nicotine is not immediate as it is in cocaine for example, but is instead only reinforcing once the user has become addicted. Nicotine is similar in structure to acetylcholine and is therefore capable to binding to nicotinic acetylcholine receptors (nACh), causing the opening of ion channels, allowing sodium to enter and a response in the postsynaptic neurone to be initiated. In the central nervous system nACh receptors are located on the ventral tegmental dopamine neurones and through binding of nicotine cause a release in dopamine by creating an action potential (Eric J. Nestler, 2001). Nicotine may also cause the release of endogenous opioids adding to its reinforcing nature. Nicotine also causes withdrawal symptoms, such as an agitated mood and shaking of the hands. This could lead to continued use just to remove the uncomfortable symptoms that are accompanied with withdrawal.
There is so much more that could be said on how drugs cause addiction and how the brain of an addict is altered from the normal state. The reinforcing nature of drugs is what causes people to seek the drug and to feel the need to take the drug again, as by hijacking the reward pathway our brains are fooled into thinking that the drug is good for the body and mind. This fact also demonstrates the strength of the reward pathway in its ability to unconsciously control the acts of the conscious mind. Each drug has its own mechanism in causing the release of dopamine but it is through this release that all drugs are reinforcing.
The consuming of drugs is a subjective topic. Whilst considered dangerous, drugs have been demonstrated to open the mind and make people observe the world in a fascinating and euphoric way. Some of the greatest pieces of literature in history, Alice in Wonderland to name an example, have been argued as products of the brain when under the effects of recreational drugs. What has to be understood is that there is a difference between taking and trying drugs and abusing them. It is the process of taking a drug regularly that causes long term alterations to the brain and enhances the reinforcing nature of the drug.
Eric J. Nestler, Steven E. Hyman and Robert C. Malenka, 2001, Molecular Neuropharmacology A foundation for Clinical Neuroscience, The McGraw-Hill companies, Inc. Medical Publishing Division.
Article by Lara Cornish.
Edited by Molly Campbell.